Antimuscarinic effect of tiquizium bromide in vitro and in vivo

Objective: We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic obstructive pulmonary disease (COPD). Methods: In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ for muscarinic receptor subtypes was also examined with a radioligand binding assay. Results: The pA2 value of TQZ was 8.75. The pK _i values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQZ inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) in a dose-dependent manner. The mean maximum increases in FVC and FEV₁ caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled. The FVC and FEV₁ were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed after inhalation of TQZ. Conclusion: These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients with COPD. Received: 3 April 1995/Accepted in revised form: 27 November 1995     

Possible site of bronchodilation due to inhaled procaterol aerosol in asthmatic patients

Summary We studied the effective site of an inhaled aerosol of procaterol, a ₂-selective adrenergic bronchodilator, in 8 asthmatic patients whose basal lung functions are almost within the normal range in both slow vital capacity (VC) and forced expiratory volume in one second (FEV_1.0), and are free from asthmatic attack. In patients who had received procaterol 30 min after inhalation of aerosol, there was no significant change in VC, although FEV_1.0, maximal expiratory flow at 50% VC , maximal expiratory flow at 25% VC and maximal expiratory flow at 30% VC of partial maximal expiratory flow volume curve improved significantly. On the other hand, in those who had received placebo, none of the parameters changed. Furthermore, Rl decreased and C_0.5 increased significantly during the first 5 min after inhalation of procaterol aerosol. After an interval of 5 min, Rl did not change any further, while C_0.5 continued to improve until 30 min after inhalation of procaterol. These results suggest that procaterol may first dilate the large airway and then may gradually dilate the small airway in bronchial asthma.     

硫酸镁雾化吸入辅助治疗对重症毛细支气管炎患儿气道阻力、肺功能及炎症因子的影响

目的 观察硫酸镁雾化吸入辅助治疗对重症毛细支气管炎患儿气道阻力、肺功能及炎症因子的影响。方法 选择于医院治疗的重症毛细支气管炎患儿88例,以随机数字表法分组,44例患儿为探究组,采用硫酸镁雾化吸入辅助常规治疗,44例患儿为参照组,采用常规治疗,两组患儿均连续治疗7 d,治疗前、后检测两组患儿炎症指标：肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、可溶性血管细胞黏附分子1(soluble vasccular cell adhesion molecule-1,sVCAM-1)、Nod样受体蛋白3(Nod-like receptor pyrin domain3,NLRP3)、嗜酸粒细胞阳离子蛋白(eosinophil cationic protein, ECP)水平：气道阻力指标：近端气道黏性阻力(R20)、气道总阻抗(Z5)、气道总黏性阻力(R5)、肺神经源性P物质水平;肺功能指标：有效呼吸道阻力(Reff)、第1秒用力呼气容积(forced expiratory volume in one second, FEV1)、最大呼气中段流量(maximal mi...     

Severe rhinosinusitis

Rhinosinusitis is diagnosed frequently in clinical practice, but the term may in fact encompass a wide spectrum of diseases. Inflammation of the nasal and sinus mucosa can arise from various causes and lead to different sequelae. Moreover, the term rhinosinusitis is more accurate than sinusitis. Causes range from a viral infection leading to the common cold to an invasive, fungal infection. An accurate diagnosis is important because effective therapy is available if recognized early and if specific therapy is used. Importantly, there is a close relationship between upper and lower airway disease and each have unique structural and functional differences that make an understanding of rhinosinusitis important not only for upper airway disease, but also for the management of asthma. All too often, rhinosinusitis becomes chronic and this becomes a challenge because medical therapy may not be sufficient to control disease. Finally, we should note that the differential diagnosis of rhinosinusitis is extensive and physicians should place heavy emphasis not only on the history, but also on appropriate imaging studies. A normal exam does not rule out the possibility or rhinosinusitis. Finally, we should emphasize that effective treatment is dependent on the etiology of the symptoms but also dependent on whether it is acute or chronic.     

An Automated Self‐Similarity Analysis of the Pulmonary Tree of the Sprague–Dawley Rat

We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague–Dawley rat. Our work is motivated by a need to inform lower‐dimensional mathematical models to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age‐matched, male Sprague–Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared with nearly 1,000 measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.     

Airway responses to antigen challenge in allergic rhinitis and allergic asthma

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively. The remaining subjects showed a less than 35% decrease in SGaw ("nonreactors") with mean relative decreases of 9% (allergic asthma) and 6% (allergic rhinitis). Mean Visov increased in all subjects with bronchial asthma and in eight of 11 subjects with allergic rhinitis. A significant increase in FRC (6%) was seen only in the "reactors" with bronchial asthma. Following antigen challenge, the beta adrenergic agonist, isoetharine, increased SGaw and decreased Visov. We conclude that in asymptomatic subjects with ragweed hypersensitivity, (1) central and peripheral airway function is more abnormal in subjects with bronchial asthma than in subjects with allergic rhinitis, (2) subjects of both groups show quantitatively and qualitatively comparable airway responses during antigen challenge with a decrease in SGaw or an increase in Visov, possibly representing increase in central and/or peripheral airflow resistance, respectively, (3) Visov may be a more sensitive indicator of airway response to antigen challenge than SGaw, and (4) the bronchodilator effects of a beta adrenergic agonist on antigen-induced bronchospasm are similar in both groups.     

The external laryngeal nerve: surgical and anatomic considerations. Report of 50 total thyroidectomies

This surgical anatomy study aimed to evaluate the possibility of identifying the external laryngeal nerve during thyroid surgery and the possible variations of nerves at risk. Fifty patients underwent total thyroidectomies during a period of 12 months. Using a neurostimulator, the distal motor branch of the external laryngeal nerve was searched. Electrical stimulation of a nervous branch aimed to provoke a global contraction of the cricothyroid in order to identify with certitude the external laryngeal nerve. The external laryngeal nerve was identified in 20% of cases. Its course was, with almost equal frequency, either (1) between the vessels of the superior thyroid pedicle or (2) superficial and anterior to the fascia of the cricothyroid muscle. The external laryngeal nerve is hard to find during thyroid surgery, even with a neurostimulator. It can be vulnerable during thyroid surgery but only in cases of anatomic variations. Searching for the nerve systematically during thyroid surgery does not seem to be useful. Several precautions when dissecting the superior pole of the thyroid gland seem to be necessary and sufficient to respect the external laryngeal nerve.     

Effect of inhaled corticosteroid on an immunoreactive thymus and activation-regulated chemokine expression in the bronchial biopsies from asthmatics

BACKGROUND: Bronchial asthma is characterized by airway inflammation, notably because of eosinophils and T cells. Thymus and activation-regulated chemokine (TARC) is known to selectively attract Th2 cells, and is increased in response to interleukin (IL)-4 and IL-13, which share a common receptor, IL-4 receptor alpha (IL-4Ralpha). While corticosteroids have proven, very effective in modifying airway inflammation, the effect of corticosteroids on TARC in asthmatics has been little studied. OBJECTIVE: We examined the effects of inhaled budesonide (BUD) on the expression of TARC and the number of inflammatory cells in bronchial biopsy specimens taken from asthma patients. METHODS: Inhaled BUD 800 mug daily, or placebo was administered for 3 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined by immunocytochemistry. RESULTS: We observed a significant decrease in the epithelial expression of TARC (P < 0.01) in the BUD group compared with the placebo group. This was accompanied by decreases in the number of eosinophils (P < 0.01), CD3(+) T cells (P < 0.05), and CD4(+) T cells (P < 0.01). A significant correlation was found between changes in epithelial TARC and in IL-4Ralpha immunoreactivity (r(s) = 0.66, P < 0.01). CONCLUSIONS: These findings suggest that corticosteroid asthma treatment can reduce infiltration of the airway by inflammatory cells, an effect modulated by down-regulation of bronchial epithelial TARC expression.     

Effect of ozone exposure on allergic sensitization and airway inflammation induced by dendritic cells

BACKGROUND: Epidemiological studies suggest that ozone exposure is related to increased asthma symptoms. Dendritic cells (DCs) are the principal antigen-presenting cells in the airways. OBJECTIVE: We have examined whether ambient doses of ozone (100 ppb for 2 h) enhance allergic sensitization and/or airway inflammation in a mouse model. METHODS: C57BL/6 mice were sensitized to inhaled ovalbumin (OVA) by intratracheal instillation of OVA-pulsed DCs on day 0. Daily exposure to OVA aerosol on days 14-20 resulted in an eosinophilic airway inflammation, as reflected in bronchoalveolar lavage fluid and lung histology. In a first experiment, mice were exposed to ozone or room air immediately prior to and following sensitization. Subsequently, we tested the effect of ozone exposure during antigen challenge in DC-sensitized mice. RESULTS: Exposure to ozone during sensitization did not influence airway inflammation after subsequent allergen challenge. In contrast, in sensitized mice, challenge with OVA together with ozone (days 14-20) resulted in enhanced airway eosinophilia and lymphocytosis, as compared with mice exposed to OVA and room air (1.91 x 106 +/- 0.46 x 106 vs. 0.16 x 106 +/- 0.06 x 106 eosinophils/mL lavage fluid; P = 0.015; 0.49 x 106 +/- 0.11 x 106 vs. 0.08 x 106 +/- 0.03 x 106 lymphocytes/mL lavage fluid; P = 0.004). Ozone exposure without subsequent OVA exposure did not cause airway inflammation. CONCLUSION: Ozone exposure does not increase allergic sensitization but enhances antigen-induced airway inflammation in mice that are sensitized via the airways.